The susceptibility of newborns to recurrent episodes of virus-induced wheezing and atopic disorders (such as asthma) has been associated with a combination of genetic and environmental factors that favor the generation of T helper 2 (Th2) cells over T helper 1 (Th1) cells. In ongoing experiments, we have discovered a governing feature of human immune system ontogeny that explains Th2 dominance in utero and that may also determine the propensity of some but not all neonates to preferentially sustain Th2-type responses after birth. Thus, the fetal immune system is derived from multi-lineage hematopoietic stem/progenitor cells (HSPCs) that give rise to tolerogenic regulatory T cells while the adult immune system is derived from distinct HSPCs that are more likely to give rise to immunoreactive T effector cells. We hypothesize that different neonates may have varying proportions of these two compartments and that those with a higher proportion of the fetal compartment may be more predisposed to sustaining Th2 responses for a longer period of time after birth. This hypothesis will be addressed in experiments of the following Specific Aims: (1) to confirm and extend previous findings that there are gene expression and functional differences that distinguish fetal and adult myeloid cells; (2) to determine whether there is inter individual variation in the admixture of fetal and adult T and/or myeloid cells in normal umbilical cord blood (UCB) samples; and (3) to determine whether skewed fetal-to-adult T and/or myeloid cell ratios in UCB are predictive of the development of viral respiratory illness and atopic disorders, e.g. asthma. These experiments should lead to a better understanding of the pathophysiology of viral respiratory illnesses and atopic disorders of childhood, and may also generate novel insights important for the diagnosis and treatment of such diseases.